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The Who's Who entry establishes that the Asylum was named after Elizabeth Arkham, the mother of founder Amadeus Arkham. The original name of the asylum was Arkham Hospital. Its dark history began in the early 1900s when Arkham's mother, having suffered from mental illness most of her life, committed suicide (It was later revealed that her son actually euthanized her, and repressed the memory). Amadeus Arkham decided, then, as the sole heir to the Arkham estate, to remodel his family home in order to properly treat the mentally ill, so others might not suffer as his mother had. Prior to the period of the hospital's remodeling, Arkham treated patients at the State Psychiatric Hospital in Metropolis, where he and his wife, Constance, and daughter, Harriet, had been living for quite some time.

Upon telling his family of his plans, they moved back to his family home to oversee the remodeling. While there, Arkham received a call from the police notifying him that serial killerMartin "Mad Dog" Hawkins — referred to Arkham by Metropolis Penitentiary while at State Psychiatric Hospital — had escaped from prison, and sought his considered opinion on the murderer's state of mind. Shortly afterward, Arkham returned to his home to find his front door wide open. Inside, he discovered the raped and mutilated bodies of his daughter and wife in an upstairs room, with Hawkins' nickname carved on Harriet's body.

The shock of the murders brings back the memory of killing his mother. For many years Elizabeth suffered delusions that she was being tormented by a supernatural creature, and would call to her son to protect her. One day, however, he finally sees what his mother saw - a great bat, a spectre of death. Taking a pearl-handled straight razor from his pocket, he cuts his mother's throat to end her suffering. He then blocks out the memory, and attributes her death to suicide.

Traumatized, Amadeus puts on his mother's wedding dress and takes out the pearl-handled razor. It is vaguely implied that Arkham, cannibalises his family's remains in a shamanic ritual.[1] Kneeling in the blood of his family, he vows to bind the evil spirit of "The Bat", which he believes inhabits the house, through ritual and sorcery. He treats Hawkins for months until finally electrocuting him in a shock therapy session. This incident is treated as an accident by the authorities. Soon after, Arkham freefalls into madness. He continues his mission even after he is incarcerated in the Asylum himself; he scratches the words of the binding spell into the walls and floor of his cell with his fingernails until the day he dies.

Dr. Cavendish, another doctor in the asylum, believes he is a reincarnation of Amadeus and frees the inmates. Towards the end of the story he takes another doctor, Dr. Adams, hostage, dresses himself in the dress of Amadeus's mother, and relates Arkham's history to Batman before attempting to strangle Batman. Dr. Adams saves Batman by killing Cavendish with the same razor Amadeus used to kill his mother.

Amadeus's role in creating the asylum, Mad Dog's history with Amadeus, and Amadeus's murder of Mad Dog and descent into madness, have become canon, and are the origin of Arkham Asylum in all incarnations of the asylum since.

In The New 52 (a reboot of the DC Comics universe), Amadeus Arkham was shown to have been the partner of the bounty hunterJonah Hex. Amadeus was a psychologist who specializes in criminal behavior and lived in a mansion with his mother. Amadeus often partners up with Jonah Hex in an effort to solve a series of murders that were committed by the Gotham Ripper and even uncovered a child slavery operation run by Thurston Moody of the Court of Owls.[2]

The spirit of Dr. Amadeus Arkham was featured in Batman: Arkham Asylum voiced by Tom Kane. The spirit of Arkham is unlocked by scanning several tablets scattered around Arkham, supposedly by Amadeus himself. They retell the story of Amadeus euthanizing his mother, the death of wife and daughter by Mad Dog, Mad Dog's death at the hands of Arkham's guards, and finally Amadeus' descent into madness. It is hinted (and later confirmed) that Warden Quincy Sharp, who believes that he is Amadeus reincarnated, is responsible for the messages as evidenced by his attempts to kill Poison Ivy, Killer Croc, Joker, and Harley Quinn being recorded onto the tablets. While there is no knowledge as to how he attempted to kill them, Sharp mentions his plans to lobotomize Harley and attempt to kill Joker in his sleep, which is thwarted by the Scarecrow. If Batman scans all the tablets and comes back to the security office where he left Quincy Sharp, he will find in his place a final message telling Batman to continue his work. Amadeus' cell can also be found in the game, the entirety of its walls and floor covered with binding circles as in Arkham Asylum: A Serious House on Serious Earth.

In Batman: Arkham City, it is revealed that Sharp's delusions of being Arkham's reincarnation were the result of drugs and hypnotherapy delivered by Dr. Hugo Strange with the help of Mad Hatter. Scanning items related to certain inmates reveal that Sharp had treated the inmates abusively, notably by locking Mad Hatter in the physically lowest cell in the Asylum with the clear intent of him never getting out (whether he meant to kill him is unclear), and again trying to murder Poison Ivy by locking her in a cell and letting her die of her Titan overdose caused by the Joker only for a priest covered in pollen to give Ivy the needed ingredients from the pollen to heal herself. Listening to the Blackgate inmates shows that some of them are aware of Sharp's inhumane treatments towards his patients (having occasionally been victims themselves) as well as Sharp often murdering his patients.